The proposed studies are designed to elucidate the role of lung cells in the generation of local host defenses, in maintenance of pulmonary homostasis, and in the pathophysiology of inflammatory lung diseases. The molecular control of synthesis, secretion will be studied in tissue culture and under cell free conditions. The products (complement, histamine catabolic enzymes) will be assayed with functional and immunochemical methods. Control of synthesis and post translational processing of the lung cell products will be studied using methods developed in this laboratory. The effect of this control on other cell functions (e.g. alveolar macrophage mediated cytotoxicity) will be investigated. Preliminary data from studies of a experimental animal and clinical investigations suggests that biochemical changes associated with pulmonary inflammation are detectable in primary cell cultures. Together with the proposed biochemical studies and methods for long term maintenance of cell in culture, pulmonary inflammation can be understood on a molecular basis. An understanding of the network of cells and humoral factors that regulate lung cell function should ultimately permit a rational approach to the treatment of pulmonary diseases.